BLOOD TYPES; TRANSFUSION; AND ➢​ Relative Frequencies of Blood Types:​

TISSUE AND ORGAN TRANSPLANTATION Based on the prevalence in a studied group, the
frequency of blood types is as follows:
○​ O: 47%
○​ A: 41%
○​ B: 9%
○​ AB: 3%​
The O and A alleles are more common,
while the B allele is less frequent.

ANTIGENICITY CAUSES IMMUNE REACTIONS OF

BLOOD
Blood transfusions require careful matching of blood types to
avoid dangerous immune reactions. The O-A-B and Rh
antigen systems are the primary factors that determine
compatibility, with the presence of specific antibodies in the
plasma potentially causing serious transfusion complications if
mismatched.

O-A-B BLOOD TYPES

The ABO blood group system plays a crucial role in blood
transfusion compatibility. Understanding the genetic
A AND B ANTIGENS—AGGLUTINOGENS
inheritance of the A, B, and O alleles helps predict blood type,
which is essential for preventing immune reactions during
The ABO blood group system is determined by the presence
transfusions. The prevalence of different blood types varies,
or absence of two main antigens, type A and type B, on the
with O and A being more common than B and AB.
surface of red blood cells (RBCs). These antigens play a key
role in blood transfusion reactions, as they can cause the
agglutination (clumping) of RBCs. The genetic inheritance of
AGGLUTININS
these antigens results in four major blood types: O, A, B, and
AB. The immune system's response to the presence or absence of
certain blood group antigens plays a critical role in the
➢​ Major O-A-B Blood Types​
development of agglutinins—antibodies that can react with
The classification of blood into four types is based on
foreign agglutinogens. These antibodies are essential for blood
the presence or absence of the A and B
type compatibility and are produced in individuals who lack
agglutinogens:
specific agglutinogens on their red blood cells (RBCs).
○​ Type O – Neither A nor B agglutinogen is
present.
○​ Type A – A agglutinogen is present.
○​ Type B – B agglutinogen is present.
○​ Type AB – Both A and B agglutinogens are
present.
➢​ Genetic Determination of Agglutinogens​
The ABO blood group is determined by three alleles
IA, IB, and IO. These alleles control the presence of
A and B agglutinogens on RBCs.
○​ The O allele (IO) is recessive and does not
produce functional agglutinogens.
○​ The A (IA) and B (IB) alleles are dominant
and produce A and B agglutinogens,
respectively.
○​ Co-dominance is exhibited between the A
and B alleles, meaning that if both are
present, both will be expressed (AB blood ➢​ Development of Agglutinins
type).​ ○​ Type O Blood – Contains both anti-A and
There are six possible genotypes that can anti-B agglutinins in the plasma, as it has
determine a person's blood type: OO, OA, neither type A nor type B agglutinogens on
OB, AA, BB, and AB. the RBCs.
➢​ Blood Type Genotypes ○​ Type A Blood – Contains type A
○​ OO genotype → Type O blood (no agglutinogens on RBCs and anti-B
agglutinogens). agglutinins in the plasma.
○​ OA or AA genotype → Type A blood (A ○​ Type B Blood – Contains type B
agglutinogens). agglutinogens on RBCs and anti-A
○​ OB or BB genotype → Type B blood (B agglutinins in the plasma.
agglutinogens). ○​ Type AB Blood – Contains both type A and
○​ AB genotype → Type AB blood (both A and type B agglutinogens on RBCs but lacks
B agglutinogens). anti-A and anti-B agglutinins.
➢​ Titer of Agglutinins​
The production of agglutinins begins after birth.

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 Initially, the quantity of agglutinins in the plasma is formation of pores in the cell membrane, resulting in
almost nonexistent. Around 2 to 8 months after birth, osmotic lysis of the RBCs.​
infants start producing anti-A and anti-B agglutinins Acute hemolysis is less common than agglutination
depending on the absence of the corresponding followed by delayed hemolysis, as it requires a high
agglutinogens in their RBCs. The maximum titer is titer of antibodies and is typically mediated by IgM
usually reached between 8 and 10 years of age and antibodies (hemolysins), which are more effective at
declines gradually with age.​ activating the complement system.
A graphical representation (Figure 36-1) illustrates
the changing titers of anti-A and anti-B agglutinins Mismatched blood transfusions can cause significant damage
over time. to the circulatory system through agglutination and hemolysis.
➢​ Origin of Agglutinins​ Understanding these reactions is critical for preventing
Agglutinins are gamma globulins (antibodies), transfusion-related complications and ensuring the safety of
primarily of the IgM and IgG immunoglobulin types. blood transfusions.
They are produced by bone marrow and lymphoid
cells, similar to other antibodies. The origin of these BLOOD TYPING
agglutinins remains a topic of interest, with one
theory suggesting that small amounts of A and B Before administering a blood transfusion, it is essential to
antigens are introduced into the body through food, determine the blood type of both the donor and the recipient to
bacteria, or other sources. These antigens stimulate ensure proper matching and prevent adverse reactions. This
the formation of anti-A and anti-B agglutinins.​ process, known as blood typing and blood matching, helps to
For example, the infusion of group A antigen into a identify the presence or absence of specific agglutinogens on
non-A recipient can lead to the production of red blood cells (RBCs) and ensures that no incompatible blood
increased anti-A agglutinins. is transfused.

Agglutinins play a crucial role in blood type compatibility and ➢​ Blood Typing Process​
immune responses. Their production, which starts after birth, Blood typing involves separating the RBCs from the
is influenced by the presence or absence of specific blood plasma and diluting them with saline solution. One
group antigens. The understanding of agglutinins' portion of the RBCs is then mixed with anti-A
development and origin is essential for managing blood agglutinin, and another portion is mixed with anti-B
transfusions and avoiding transfusion reactions. agglutinin. After allowing time for the reactions to
occur, the mixtures are observed under a microscope.
AGGLUTINATION PROCESS IN TRANSFUSION If the RBCs become clumped (agglutinated), it
REACTIONS indicates that an antibody-antigen reaction has
occurred.
Mismatched blood transfusions can trigger severe immune ➢​ Interpretation of Results​
reactions, such as agglutination and hemolysis of red blood The presence or absence of agglutination reveals the
cells (RBCs). These reactions occur when plasma antibodies blood type
(anti-A or anti-B agglutinins) interact with RBCs containing ○​ Type O RBCs – No agglutinogens are
corresponding agglutinogens (A or B). The subsequent present, so they do not react with either
clumping of RBCs can lead to a variety of complications, anti-A or anti-B agglutinins.
including blockage of blood vessels and the release of ○​ Type A RBCs – These contain A
hemoglobin into the plasma. agglutinogens, causing them to agglutinate
when mixed with anti-A agglutinins.
➢​ Agglutination Process​ ○​ Type B RBCs – These contain B
When anti-A or anti-B agglutinins in plasma are agglutinogens, leading to agglutination
mixed with RBCs that contain the corresponding when mixed with anti-B agglutinins.
agglutinogens (A or B), the agglutinins attach to the ○​ Type AB RBCs – Both A and B
RBCs. These antibodies can bind to multiple RBCs agglutinogens are present, so these RBCs
simultaneously, causing them to clump together. This agglutinate with both anti-A and anti-B
process, known as agglutination, leads to the agglutinins.
formation of large clumps of RBCs that can obstruct
small blood vessels throughout the circulatory
system.
➢​ Hemolysis​
After agglutination, the clumped RBCs can be
physically distorted or attacked by phagocytic white
blood cells, leading to their destruction. This
destruction results in the release of hemoglobin into
the plasma, a process called hemolysis. Hemolysis
can have serious consequences for the recipient's
health, as it disrupts the normal circulation of oxygen
and can lead to organ damage.
➢​ Acute Hemolysis in Mismatched Transfusions​
In some cases, mismatched blood transfusions can Blood typing is a crucial step in ensuring the safety of blood
lead to immediate hemolysis of RBCs in the transfusions. By carefully matching the donor’s and recipient’s
circulating blood. The agglutinin antibodies activate blood types, healthcare providers can prevent harmful immune
the complement system, leading to the formation of a reactions and guarantee the success of the transfusion.
membrane attack complex (MAC), which inserts
itself into the lipid bilayer of RBCs. This causes the Rh BLOOD TYPES

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In addition to the O-A-B blood type system, the Rh blood type sensitized to the Rh factor, leading to a stronger
system plays a significant role in blood transfusions. Unlike immune response.
the O-A-B system, where agglutinins develop spontaneously, ➢​ Characteristics of Rh Transfusion Reactions
the Rh system typically requires prior exposure to Rh antigens ○​ First Exposure​
before significant transfusion reactions can occur. If an Rh-negative person receives
Rh-positive blood for the first time, they
➢​ Rh Antigens​ typically will not experience an immediate
The Rh system includes six common types of transfusion reaction. However, the immune
antigens, each known as an Rh factor. These are system starts developing anti-Rh antibodies,
designated as C, D, E, c, d, and e. If a person has the which can lead to delayed agglutination and
C antigen, they will not have the c antigen, and hemolysis of the transfused red blood cells
similarly, those with the D antigen will not have the d (RBCs) over the next 2 to 4 weeks. This
antigen. The D antigen is the most common and reaction is usually mild but involves the
antigenic of the Rh factors. macrophage system, which removes the
➢​ Rh-Positive and Rh-Negative agglutinated RBCs.
○​ Rh-Positive – A person who has the D ○​ Subsequent Exposures​
antigen is considered Rh positive. Upon further exposure to Rh-positive blood,
○​ Rh-Negative – A person lacking the D the individual who has already developed
antigen is considered Rh negative. Though anti-Rh antibodies will experience a
Rh-negative individuals may still have other significantly stronger and faster immune
Rh antigens, these tend to cause milder response. The reaction can be severe, as the
transfusion reactions compared to the D antibodies rapidly attack and destroy the
antigen. transfused Rh-positive RBCs. This reaction
➢​ Rh Sensitization​ can be as intense as a transfusion mismatch
Unlike the O-A-B system, where individuals between type A and type B blood.
naturally produce antibodies (agglutinins) to antigens
absent from their own red blood cells, Rh-negative The development of anti-Rh agglutinins is a critical factor in
individuals typically do not produce antibodies to the Rh-negative individuals receiving Rh-positive blood. The first
Rh antigen unless they are exposed to Rh-positive exposure may cause mild delayed reactions, but subsequent
blood, such as during a transfusion. This exposure transfusions can lead to severe and immediate transfusion
can lead to sensitization, making subsequent reactions. This highlights the importance of accurate blood
transfusions more likely to cause a severe reaction. matching and awareness of Rh status in transfusion practices
➢​ Rh Blood Type Distribution to avoid life-threatening complications.​
○​ In whites, approximately 85% are Rh
positive, and 15% are Rh negative.
○​ In American blacks, 95% are Rh positive. ERYTHROBLASTOSIS FETALIS (HEMOLYTIC DISEASE
○​ African blacks and people of Asian OF THE NEWBORN)
descent (including those from China, Japan,
and Korea) have Rh-positive rates close to Erythroblastosis fetalis is a serious condition that affects the
100%. fetus and newborn, characterized by the agglutination and
○​ Globally, it is estimated that 95% of people phagocytosis of red blood cells (RBCs). This disease typically
are Rh positive, and around 6% are Rh occurs when an Rh-negative mother carries an Rh-positive
negative. fetus, and it is caused by the mother’s immune system reacting
against the Rh antigen on the fetus’s RBCs.
The Rh system is an important consideration in blood
transfusions. Although the Rh-negative condition requires ➢​ Incidence of Erythroblastosis Fetalis​
prior exposure to Rh-positive blood for a reaction to occur, An Rh-negative mother carrying her first Rh-positive
careful matching of blood types, including the Rh factor, is baby usually does not develop enough anti-Rh
essential to prevent potentially dangerous transfusion antibodies to cause significant harm. However, the
reactions. risk increases with subsequent pregnancies, with the
incidence rising progressively as follows:
Rh IMMUNE RESPONSE ○​ Second child – 3% of cases show signs of
the disease
The formation of anti-Rh agglutinins and the subsequent ○​ Third child – 10% of cases
reactions when an Rh-negative person is exposed to ○​ Subsequent pregnancies – The risk
Rh-positive blood is a critical consideration in transfusion continues to increase.
medicine. Rh-negative individuals, upon exposure to ➢​ Effect of Mother’s Antibodies on the Fetus​
Rh-positive blood, can develop immune responses that After forming anti-Rh antibodies, they diffuse
increase the risk of severe transfusion reactions with future through the placenta into the fetus’s bloodstream.
exposures. Once in the fetus’s blood, the antibodies cause
agglutination of RBCs, which leads to hemolysis
➢​ Formation of Anti-Rh Agglutinins​ (destruction) of the RBCs. The hemoglobin released
When an Rh-negative person is exposed to blood from these cells is converted into bilirubin by the
containing the Rh factor, such as during a transfusion fetus’s macrophages. High bilirubin levels cause
of Rh-positive blood, their immune system begins to jaundice, which is a characteristic sign of
produce anti-Rh antibodies (agglutinins). This erythroblastosis fetalis. In addition to affecting the
response is gradual, reaching its peak about 2 to 4 blood cells, the antibodies can also damage other
months after exposure. The degree of this immune cells in the fetus’s body.
response can vary among individuals. With repeated
exposure, the person may become increasingly
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 ➢​ Clinical Picture of Erythroblastosis Fetalis​ ○​ Hemoglobin released during hemolysis is
The newborn typically presents with severe anemia converted into bilirubin by phagocytes,
and jaundice. The presence of early-stage RBCs, which is excreted by the liver into bile.
including nucleated blastic forms, in the circulation ○​ If a significant amount of blood is
gives the disease its name, erythroblastosis fetalis. hemolyzed quickly, bilirubin levels rise,
The infant’s liver and spleen enlarge as they attempt causing jaundice (yellowing of skin and
to compensate for the loss of RBCs by producing tissues), although jaundice generally does
more. Although severe anemia often leads to death, not appear unless over 400 milliliters of
many surviving infants suffer from permanent mental blood is destroyed in less than one day.
impairment or damage to motor areas of the brain due ➢​ Acute Kidney Failure
to the accumulation of bilirubin in neuronal cells ○​ A severe outcome of transfusion reactions is
(kernicterus). acute kidney failure, which can develop
➢​ Treatment of Neonates with Erythroblastosis within hours.
Fetalis​ ○​ Three main factors contribute to kidney
One treatment option is to perform an exchange shutdown:
transfusion, where the infant’s Rh-positive blood is ■​ Toxic substances from hemolyzed
replaced with Rh-negative blood. This process helps blood cause renal vasoconstriction,
lower bilirubin levels and prevent kernicterus. The reducing blood flow to the kidneys.
procedure may be repeated several times over the ■​ Circulatory shock, with low blood
first few weeks of life, and by the time the infant’s pressure and decreased renal blood
own Rh-positive RBCs replace the transfused flow, exacerbates kidney damage.
Rh-negative blood, the anti-Rh agglutinins from the ■​ Free hemoglobin released from
mother will have been destroyed. destroyed RBCs exceeds the
➢​ Prevention of Erythroblastosis Fetalis​ capacity of haptoglobin to bind it,
The development of Rh immunoglobulin (anti-D leading to excess hemoglobin
antibody) has greatly reduced the incidence of entering kidney tubules and causing
erythroblastosis fetalis. Administering this antibody blockage.
to Rh-negative mothers at 28 to 30 weeks of gestation ○​ These factors combined lead to acute renal
and following childbirth, when they deliver failure, which can result in death if left
Rh-positive babies, prevents the mother from untreated.
becoming sensitized to the Rh factor. This
intervention blocks the immune response to the Rh Transfusion reactions can cause severe health issues, including
antigen, thus preventing the formation of harmful hemolysis, jaundice, and acute kidney failure. Prompt
anti-D antibodies in subsequent pregnancies. intervention, such as kidney dialysis, is critical in preventing
death from renal shutdown. Proper blood matching and careful
Erythroblastosis fetalis is a serious but preventable condition monitoring are essential to avoid these potentially
caused by the immune system’s reaction to Rh-positive blood life-threatening complications.
in an Rh-negative mother. Advances in treatment, such as
exchange transfusions, and preventive measures, like the TRANSPLANTATION OF TISSUES AND ORGANS
administration of Rh immunoglobulin, have significantly
reduced the incidence of this disease, safeguarding the health Transplantation of tissues and organs from one individual to
of newborns. another can trigger immune reactions, as the body recognizes
foreign cells as potential threats. Different types of grafts,
TRANSFUSION REACTIONS RESULTING FROM based on the source of the transplanted tissue, vary in their
MISMATCHED BLOOD TYPES likelihood of immune rejection.

Blood transfusions between incompatible blood types can lead ➢​ Types of Grafts
to serious reactions in the recipient. These reactions involve ○​ Autografts – Tissue or organs transplanted
agglutination of the donor’s red blood cells (RBCs), followed from one part of the same animal to another
by a series of complications that may affect various organs, part. These typically face minimal rejection
including the kidneys. Understanding the mechanisms and since the cells have the same antigens as the
outcomes of transfusion reactions is crucial in preventing recipient’s tissue.
severe health consequences. ○​ Isografts – Transplants between genetically
identical individuals, such as identical twins.
➢​ Transfusion Reaction Process These grafts also usually do not face
○​ When mismatched blood is transfused, the immune rejection.
recipient’s agglutinins (antibodies) target the ○​ Allografts – Transplants between
donor’s RBCs, causing agglutination. individuals of the same species but
○​ The donor's plasma is diluted in the genetically different, such as from one
recipient's plasma, which lowers the titer of person to another. These are more prone to
agglutinins, making it rare for donor blood immune rejection but can be successful with
to agglutinate the recipient's RBCs. proper matching.
○​ However, the recipient's agglutinins can still ○​ Xenografts – Transplants between different
cause the agglutination of donor RBCs, species, such as from animals to humans.
leading to further complications. These grafts usually face rapid rejection
➢​ Hemolysis and Bilirubin Production unless treated with specific therapies.
○​ Agglutinated RBCs are eventually ➢​ Immune Reactions in Transplants
hemolyzed (destroyed) either immediately ○​ In autografts and isografts, the transplanted
or through phagocytosis. tissue contains similar antigens as the

4
 recipient’s own tissues, leading to a high ○​ Using genetic testing, doctors can achieve
likelihood of successful integration. the best possible match, improving
○​ Allografts, while more likely to face transplant outcomes and reducing the risk of
immune rejection, can still be successful if rejection.
there is proper tissue matching and ➢​ Best Matches
immunosuppressive therapy. ○​ The best success in tissue typing has been
○​ Xenografts face significant challenges due observed in transplants between siblings and
to the presence of foreign antigens, and between parent and child due to closer
without intervention, the cells in the graft genetic similarity.
often die within a short period after ○​ Identical twins have the exact same HLA
transplantation (1 day to 5 weeks). antigens, so transplants between them are
➢​ Successful Transplants almost never rejected.
○​ Several types of cellular tissues and organs,
such as skin, kidney, heart, liver, bone Tissue typing has significantly improved the success rates of
marrow, and lungs, have been transplanted organ and tissue transplants by matching HLA antigens
as allografts. between donor and recipient. While a perfect match is ideal,
○​ With appropriate matching and advancements in genetic testing have made transplants safer,
immunosuppressive treatments, many particularly between closely related individuals or identical
kidney allografts can function for 5 to 15 twins. These methods are crucial in minimizing the risk of
years, and liver and heart transplants can immune rejection and improving the long-term success of
last 1 to 15 years. transplants.

Transplantation success is largely dependent on the type of PREVENTION OF GRAFT REJECTION BY

graft and the body's immune response. Autografts and SUPPRESSING THE IMMUNE SYSTEM
isografts have the best success rates due to their genetic
similarity, while allografts and xenografts require careful For organ transplantation to be successful, especially when the
management to prevent rejection. Advances in immunology donor and recipient are not genetically identical, the immune
and tissue matching continue to improve the outcomes of system must be suppressed to prevent graft rejection. Various
organ transplantation. therapeutic agents are used to suppress immune responses, but
this suppression comes with risks, such as increased
ATTEMPTS TO OVERCOME IMMUNE REACTIONS IN vulnerability to infections and cancer. The goal of
TRANSPLANTED TISSUE immunosuppressive therapy is to find a balance between
preventing rejection and minimizing harmful side effects.
To improve the success rates of organ and tissue transplants,
various methods have been developed to prevent ➢​ Suppression of the Immune System
antigen-antibody reactions that can lead to graft rejection. One ○​ If the immune system were completely
of the most important procedures in this regard is tissue suppressed, graft rejection would not occur.
typing, which identifies key antigens responsible for immune In some cases, severe immune system
responses during transplantation. depression can allow grafts to survive
without significant intervention.
➢​ Human Leukocyte Antigen (HLA) Complex ○​ However, in individuals with a healthy
○​ The key antigens involved in graft rejection immune system, even with perfect tissue
are HLA antigens, which are located on the matching, allografts often face rejection
membranes of tissue cells and white blood within days or weeks without
cells. immunosuppressive therapy.
○​ Each person has six of these HLA antigens, ○​ T cells are the primary immune cells
but there are approximately 150 different responsible for attacking grafted tissue,
HLA antigens, resulting in over 1 trillion making their suppression more critical than
possible combinations. suppressing plasma antibodies.
○​ Except for identical twins, it is highly ➢​ Immunosuppressive Agents​
unlikely that two individuals will have the Several drugs are used to suppress the immune
same HLA antigen set, making graft system and prevent graft rejection:
rejection a significant concern for most ○​ Glucocorticoids – These hormones inhibit
transplants. the production of interleukin-2 (IL-2), a
➢​ Tissue Typing Process cytokine that stimulates T-cell proliferation
○​ Tissue typing is performed by isolating and antibody formation.
lymphocytes (a type of white blood cell) ○​ Azathioprine – A drug that has a toxic
from the donor and recipient’s blood. effect on the lymphoid system, blocking the
○​ These lymphocytes are then mixed with formation of antibodies and T-cells.
antisera and complement and tested for ○​ Cyclosporine and Tacrolimus – These
membrane damage, typically by checking drugs inhibit the formation of T-helper
the rate of dye uptake by the lymphocytes, cells, specifically targeting the T-cell
to identify compatibility. rejection response, without severely
➢​ Antigen Compatibility affecting other immune functions.
○​ Not all HLA antigens are strongly antigenic, ○​ Immunosuppressive Antibodies – Specific
meaning a precise match of all antigens antibodies, such as antilymphocyte or IL-2
between donor and recipient is not always receptor antibodies, are also used to
necessary for successful graft acceptance. prevent immune rejection.
➢​ Risks of Immunosuppressive Therapy

5
 ○​ While effective in preventing graft rejection,
these therapies leave patients vulnerable to
infections, as their immune systems are
weakened.
○​ The risk of cancer is also increased in
immunosuppressed individuals, likely
because the immune system is less effective
at detecting and destroying early cancer
cells.

Immunosuppressive therapy has made successful organ

transplantation much more common by preventing graft
rejection. However, these drugs come with significant risks,
such as increased susceptibility to infections and cancer. The
challenge of modern immunosuppressive therapy is to strike a
balance between preventing rejection and limiting the adverse
effects on the immune system.